Src is activated by the nuclear receptor peroxisome proliferator‐activated receptor β/δ in ultraviolet radiation‐induced skin cancer. Issue 1 (6th November 2013)

• Record Type: Journal Article
• Authors: Montagner, Alexandra; Delgado, Maria B; Tallichet‐Blanc, Corinne; Chan, Jeremy S K; Sng, Ming K; Mottaz, Hélène; Degueurce, Gwendoline; Lippi, Yannick; Moret, Catherine; Baruchet, Michael; Antsiferova, Maria; Werner, Sabine; Hohl, Daniel; Al Saati, Talal; Farmer, Pierre J; Tan, Nguan S; Michalik, Liliane; Wahli, Walter
• Is Part Of: EMBO molecular medicine. Volume 6:Issue 1(2014:Jan.)
• Page Start: 80
• Page End: 98
• Publication Date: 2013-11-06
• Subjects: Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.1002/emmm.201302666
• Languages: English
• ISSNs: 1757-4676

Abstract

<abstract abstract-type="main" id="emmm201302666-abs-0001"> <title>Abstract</title> <p>Although non‐melanoma skin cancer (NMSC) is the most common human cancer and its incidence continues to rise worldwide, the mechanisms underlying its development remain incompletely understood. Here, we unveil a cascade of events involving peroxisome proliferator‐activated receptor (PPAR) β/δ and the oncogene <italic>Src</italic>, which promotes the development of ultraviolet (UV)‐induced skin cancer in mice. UV‐induced PPARβ/δ activity, which directly stimulated <italic>Src</italic> expression, increased Src kinase activity and enhanced the EGFR/Erk1/2 signalling pathway, resulting in increased epithelial‐to‐mesenchymal transition (EMT) marker expression. Consistent with these observations, PPARβ/δ‐null mice developed fewer and smaller skin tumours, and a PPARβ/δ antagonist prevented UV‐dependent <italic>Src</italic> stimulation. Furthermore, the expression of <italic>PPAR</italic>β<italic>/</italic>δ positively correlated with the expression of <italic>SRC</italic> and EMT markers in human skin squamous cell carcinoma (SCC), and critically, linear models applied to several human epithelial cancers revealed an interaction between PPARβ/δ and SRC and TGFβ1 transcriptional levels. Taken together, these observations motivate the future evaluation of PPARβ/δ modulators to attenuate the development of several epithelial cancers.</p> </abstract>